Australia's national zoster vaccination program: Knowledge, attitudes and behaviour of general practitioners.

OBJECTIVES: To assess knowledge, attitudes and behaviour of Australian general practitioners (GPs) regarding herpes zoster vaccination under the National Immunisation Program (NIP) from 2016 for adults aged 70-79 years. DESIGN, SETTING, PARTICIPANTS: National cross-sectional online survey of GPs, October-November 2017. OUTCOME MEASURES: Knowledge, attitudes and behaviour regarding zoster vaccination, including challenges experienced and recommendations for improvement. RESULTS: Of the 1026 GPs who responded (response rate 7.9%), 98.5% were aware that zoster vaccine is NIP-funded for adults aged 70-79 years and 85.4% that it is recommended for age 60-69 years; however, 51.3% incorrectly thought it is routinely recommended for age 50-59 years. A minority (4.6%) incorrectly believed that being immunocompromised is not a contraindication to zoster vaccination and 16.0% that it cannot be co-administered with influenza or pneumococcal vaccine. Almost half (48.9%) rarely or never reported zoster vaccination data to the Australian Immunisation Register (AIR). Challenges perceived included lack of adequate information on vaccine contraindications; efficacy and safety concerns; and difficulty applying age criteria for NIP eligibility in general practice. Respondents indicated a desire for program expansion to include younger and older adult age groups. CONCLUSION: This Australian GP survey, conducted one year after the introduction of the national zoster vaccination program, identified some knowledge gaps. A repeat survey of GPs is warranted to determine whether these issues persist, particularly regarding contraindication to vaccination for immunocompromised individuals. We encourage all GPs to offer zoster vaccination in line with current Australian evidence-based guidelines, particularly for the NIP-funded 70-79 years cohort; ensuring compliance with relevant contraindications; and reporting to AIR.

Herpes Zoster and Its Prevention by Vaccination.

Herpes zoster (HZ; shingles) results from reactivation of varicella-zoster virus (VZV) after primary infection as varicella (chicken pox). It affects mainly older adults and people with immunocompromising diseases or treatments. The most common complication is postherpetic neuralgia (PHN), which has significant adverse effects on quality of life and activities of daily living. Since PHN cannot be prevented once HZ has occurred, and treatment is only modestly successful and is associated with significant side effects, the recent introduction of an effective vaccine is an important achievement. This new vaccine, which combines a single VZV glycoprotein (gE) and a multicomponent adjuvant, is superior to the previously available live attenuated VZV vaccine. The recombinant adjuvanted vaccine is remarkably effective in restoring the protective T cell-mediated immunity required to prevent HZ. Its clinical efficacy is much greater than that observed with other vaccines for older individuals affected by immune senescence, and its safety profile is very acceptable. It has been recommended in the USA and Canada for people who are 50 years of age and older. The immunogenicity and safety of this vaccine in severely immunocompromised individuals, such as after chemotherapy for malignancy, after solid organ or stem cell transplant, and in people with HIV are being studied.

Herpes Zoster Vaccines.

Background: Immunization for herpes zoster (HZ) aims to reverse the decline in cell-mediated immunity to varicella zoster virus that occurs with advancing age or immunocompromise. There are 2 vaccines available, one live attenuated (Zoster vaccine, live attenuated [ZVL]) and, recently, a recombinant subunit vaccine (HZ/su). Methods: The literature relevant to the two HZ vaccines was reviewed. Results: ZVL has overall efficacies of 51% and 65% against HZ and postherpetic neuralgia, respectively, with a prominent decline in efficacy with advancing age of the vaccinee. This compares to approximately 90% efficacy against HZ for HZ/su that is minimally affected with advancing age. The efficacy of ZVL against HZ declines over 4 and 8 years, compared with minimal decline so far over 4 years with HZ/su, and immunogenicity that is maintained for 9 years. Local and systemic reactogenicity to HZ/su is much greater than to ZVL. Conclusions: HZ/su establishes an important principle-that a single recombinant viral protein with an effective adjuvant combination can stimulate immunogenicity superior to that of a live attenuated vaccine, and that this can diminish immunosenescence. This provides hope for improvement of other vaccines for aging patients. However, key questions remain unanswered, including the durability of the efficacy of HZ/su, its efficacy as a booster for previous recipients of ZVL, and its efficacy in immunocompromised patients.

Use of Real-world Evidence to Evaluate the Effectiveness of Herpes Zoster Vaccine.

This article reviews the use of real-world evidence (RWE) from observational studies to evaluate herpes zoster vaccine effectiveness and complement clinical trial data that have known limitations. The use of RWE with appropriate study designs and cautious interpretation can be informative in decision-making. Understanding the advantages and limitations of studies yielding RWE can facilitate the critical evaluation of findings from different studies. This is a timely issue, as regulatory agencies are considering how RWE can contribute to the assessment of effectiveness in regulatory decision-making.

Statistical Learning Methods to Determine Immune Correlates of Herpes Zoster in Vaccine Efficacy Trials.

Using Super Learner, a machine learning statistical method, we assessed varicella zoster virus-specific glycoprotein-based enzyme-linked immunosorbent assay (gpELISA) antibody titer as an individual-level signature of herpes zoster (HZ) risk in the Zostavax Efficacy and Safety Trial. Gender and pre- and postvaccination gpELISA titers had moderate ability to predict whether a 50-59 year old experienced HZ over 1-2 years of follow-up, with equal classification accuracy (cross-validated area under the receiver operator curve = 0.65) for vaccine and placebo recipients. Previous analyses suggested that fold-rise gpELISA titer is a statistical correlate of protection and supported the hypothesis that it is not a mechanistic correlate of protection. Our results also support this hypothesis.

A post hoc analysis utilizing the FDA toxicity grading scale to assess injection site adverse events following immunization with the live attenuated Zoster Vaccine (ZVL).

BACKGROUND: ZOSTAVAX (ZVL; Zoster Virus Live), is a single dose, live, attenuated vaccine licensed for the prevention of herpes zoster (HZ) and post herpetic neuralgia (PHN) in adults ≥50 years of age. Injection site adverse events (AEs) of erythema, swelling and pain were solicited within 5 days post vaccination in the 2 pivotal studies of ZVL; ZEST (ZOSTAVAX Efficacy and Safety Trial) and SPS (Shingles Prevention Study). Protocol specified criteria were used to report the frequency and intensity of injection site AEs in ZEST and SPS studies. Subsequently, the FDA Toxicity Grading Scale provided guidance for uniform assessment of AEs across all adult vaccine clinical trials. The objective of this post-hoc analysis was to categorize the previously reported injection site AEs in two pivotal trials of ZVL according to the current FDA Toxicity Grading Scale. METHODS: The current FDA Toxicity Grading Scale provides a measure for classifying injection site AEs by four grades [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe) and Grade 4 (life threatening)]. Injection site erythema, swelling, and pain intensity gradings were assigned to the respective FDA Toxicity Grade based on this appropriation. A descriptive analysis of the proportion and risk difference (within 95% confidence intervals) of injection site AEs per the FDA Toxicity Grading Scale is provided. RESULTS: The frequency of injection site AEs (erythema, swelling, pain) after subcutaneous vaccination with ZVL were higher in recipients of ZVL compared with placebo. Majority of the injection site AEs observed were Grade 1 (mild) or Grade 2 (moderate) in intensity. Additionally, Grade 3 (severe) injection site AEs were observed infrequently. CONCLUSIONS: Application of the FDA Toxicity Grading Scale provides a uniform AE assessment tool across different adult vaccines. This post hoc summary of injection site AEs using FDA Toxicity Grading Scale provides further evidence of low frequency of severe injection site AEs post ZVL vaccination.

A randomized lot-to-lot immunogenicity consistency study of the candidate zoster vaccine HZ/su.

BACKGROUND: The risk of developing herpes zoster (HZ) increases with age and is thought to be associated with a decrease in cell-mediated immunity in older adults. The adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) recombinant subunit vaccine (HZ/su) showed >90% efficacy in the prevention of HZ when administered in adults ≥50 years of age. Here we aim to evaluate immunogenicity consistency of 3 different HZ/su vaccine lots and to assess safety of these lots. METHODS: This multicenter, phase III, double-blind, randomized study (NCT02075515), assessed lot-to-lot consistency in terms of immunogenicity of HZ/su and also assessed safety of these lots. Participants aged 50 years or older were randomized (1:1:1) to receive 2 doses of HZ/su, 2 months apart, from 1 out of 3 randomized HZ/su lots (Lots A, B and C). Humoral immunogenicity was assessed pre-vaccination and 1 month post-second vaccination by anti-gE antibody enzyme-linked immunosorbent assay. Lot-to-lot consistency was demonstrated if the 2-sided 95% confidence intervals of the anti-gE geometric mean concentration ratio between all lot pairs were within 0.67 and 1.5. Solicited symptoms were recorded within 7 days and unsolicited adverse events (AEs) within 30 days after each vaccination. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were reported until study end (12 months post-second vaccination). RESULTS: Of 651 participants enrolled in the study, 638 received both doses of the HZ/su vaccine and 634 completed the study. Humoral immune responses were robust and consistency between 3 manufacturing lots was demonstrated. The incidence of solicited symptoms, unsolicited AEs and SAEs was comparable between all lots. Three fatal SAEs, 1 in each lot, were reported, none of which were considered vaccine-related by investigator assessment. Two out of the 8 reported pIMDs were considered vaccine-related by the investigator. CONCLUSION: The three HZ/su manufacturing lots demonstrated consistent immunogenicity. No safety concerns were identified. Clinical trial registry number: NCT02075515 (ClinicalTrials.gov).

Immunizations for adult women.

Immunizations protect individual persons and contribute to public health by reducing morbidity and mortality associated with common infectious diseases. In this Practice Pearl, we review guidelines for adult immunizations and recent and potential changes in vaccines.

Physician Attitudes Toward Adult Vaccines and Other Preventive Practices, United States, 2012.

OBJECTIVES: We described the following among U.S. primary care physicians: (1) perceived importance of vaccines recommended by the Advisory Committee on Immunization Practices relative to U.S. Preventive Services Task Force (USPSTF) preventive services, (2) attitudes toward the U.S. adult immunization schedule, and (3) awareness and use of Medicare preventive service visits. METHODS: We conducted an Internet and mail survey from March to June 2012 among national networks of general internists and family physicians. RESULTS: We received responses from 352 of 445 (79%) general internists and 255 of 409 (62%) family physicians. For a 67-year-old hypothetical patient, 540/606 (89%, 95% confidence interval [CI] 87, 92) of physicians ranked seasonal influenza vaccine and 487/607 (80%, 95% CI 77, 83) ranked pneumococcal vaccine as very important, whereas 381/604 (63%, 95% CI 59, 67) ranked Tdap/Td vaccine and 288/607 (47%, 95% CI 43, 51) ranked herpes zoster vaccine as very important (p<0.001). All Grade A USPSTF recommendations were considered more important than Tdap/Td and herpes zoster vaccines. For the hypothetical patient aged 30 years, the number and percentage of physicians who reported that the Tdap/Td vaccine (377/604; 62%, 95% CI 59, 66) is very important was greater than the number and percentage who reported that the seasonal influenza vaccine (263/605; 43%, 95% CI 40, 47) is very important (p<0.001), and all Grade A and Grade B USPSTF recommendations were more often reported as very important than was any vaccine. A total of 172 of 587 physicians (29%) found aspects of the adult immunization schedule confusing. Among physicians aware of "Welcome to Medicare" and annual wellness visits, 492/514 (96%, 95% CI 94, 97) and 329/496 (66%, 95% CI 62, 70), respectively, reported having conducted fewer than 10 such visits in the previous month. CONCLUSIONS: Despite lack of prioritization of vaccines by ACIP, physicians are prioritizing some vaccines over others and ranking some vaccines below other preventive services. These attitudes and confusion about the immunization schedule may result in missed opportunities for vaccination. Medicare preventive visits are not being used widely despite offering a venue for delivery of preventive services, including vaccinations.

[Herpes zoster and postherpetic neuralgia - prevention by vaccination?]. / Herpes zoster und postherpetische Neuralgie - Vorbeugung durch Impfung?

Herpes zoster is caused by reactivation of latent varicella-zoster virus (VZV), which had remained latent in the dorsal root or cranial nerve ganglia since the primary infection. The risk of developing zoster increases significantly with age, the vast majority of zoster cases occuring in persons over 50 years. The most frequent and debilitating complication of zoster in immunocompetent patients is postherpetic neuralgia (PHN). In the absence of antiviral therapy, clinical studies have found up to 30 - 45 % of persons over 60 years of age to experience pain persisting for more than 6 months. Systemic antiviral therapy is able to shorten the healing process of acute zoster and to prevent or alleviate pain and other complications, when given within 72 hours after appearance of the rash. About 20 % of patients older than 50 years continue to have pain six months after appearance of rash, despite antiviral treatment. A live attenuated VZV vaccine was licensed in Europe in 2006 for the prevention of zoster in individuals from the age of 60 years. Findings of a large clinical trial have shown that the zoster vaccine reduced the burden of illness caused by zoster among people 60 years of age or older by 61 % and the incidence of PHN by 67 %. Compared with controls, subjects who received the vaccine were 51 % less likely to develop zoster.